Historical Management of Obstructive HCM: Limitations of Medical Therapy and Septal Reduction Access

In this segment, Dr Maron and Dr Masri dissect the historical standard of care for symptomatic obstructive HCM, centered on beta-blockers and nondihydropyridine calcium channel blockers as first-line drugs, with disopyramide often used as an adjunct. Masri notes that the evidence base for these agents has been largely constrained to expert consensus and small, non–multicenter trials. Mechanistically, these drugs act “outside the sarcomere,” aiming to blunt heart rate and contractility without directly correcting the primary sarcomeric hypercontractile defect that characterizes HCM.

Despite long-standing clinical use, Maron characterizes the efficacy of beta-blockers and calcium channel blockers as suboptimal, particularly with respect to robust, consistent LVOT gradient reduction at rest and with provocation. Disopyramide offers somewhat greater gradient lowering but is limited by anticholinergic adverse effects, tolerability concerns, and attenuated effectiveness over time. Consequently, a substantial subset of patients remains symptomatic, with incomplete relief of obstruction or inability to tolerate adequate dosing.

The faculty also discuss invasive options, including surgical septal myectomy and alcohol septal ablation, which have demonstrated excellent outcomes when performed at experienced high-volume centers. However, as Masri highlights, the global availability of truly expert centers and surgeons is limited, and referral patterns are often delayed or misaligned with symptom severity. The combined limitations of pharmacologic agents and restricted access to septal reduction therapies contributed to chronic under-treatment and clearly defined the unmet need that ultimately drove development of sarcomere-directed myosin inhibition.